The human pathogen Mycobacterium tuberculosis and the fish pathogen Mycobacterium marinum trigger the same core set of late innate immune response genes in zebrafish larvae
bioRxiv (Cold Spring Harbor Laboratory)
Abstract
Abstract Zebrafish is a natural host of various Mycobacterium species and a surrogate model organism for tuberculosis research. Mycobacterium marinum is evolutionarily one of the closest non-tuberculous species related to M. tuberculosis and shares the majority of virulence genes. Although zebrafish is not a natural host of the human pathogen, we have previously demonstrated successful robotic infection of zebrafish embryos with M. tuberculosis and performed drug treatment of the infected larvae. In the present study we examined for how long M. tuberculosis can be propagated in zebrafish larvae and tested a time series of infected larvae to study the transcriptional response via Illumina RNA deep sequencing (RNAseq). Granuloma-like structures carrying fluorescently labeled M. tuberculosis could be detected up to 9 days post infection. The continued presence of viable M. tuberculosis in the zebrafish larvae was further confirmed using the molecular bacterial load (MBL) assay. The infected larvae showed a clear and specific transcriptional immune response with a high similarity to the response of zebrafish larvae infected with the surrogate species M. marinum . We conclude that M. tuberculosis can be propagated in zebrafish larvae for at least one week after infection and provide further evidence that M. marinum is a good surrogate model for M. tuberculosis .
Authors 14
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Affiliation as printed
ZF-screens B.V., J.H. Oortweg 19
ZF-screens B.V., J.H. Oortweg 9, 2333 CH Leiden, The Netherlands
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Affiliation as printed
ZF-screens B.V., J.H. Oortweg 19
ZF-screens B.V., J.H. Oortweg 9, 2333 CH Leiden, The Netherlands
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Affiliation as printed
ZF-screens B.V., J.H. Oortweg 19
ZF-screens B.V., J.H. Oortweg 9, 2333 CH Leiden, The Netherlands
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Affiliation as printed
ZF-screens B.V., J.H. Oortweg 19
ZF-screens B.V., J.H. Oortweg 9, 2333 CH Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center
Department of Infectious Diseases, Leiden University Medical Center, 300 RC Leiden, The Netherlands
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Affiliation as printed
ZF-screens B.V., J.H. Oortweg 19
ZF-screens B.V., J.H. Oortweg 9, 2333 CH Leiden, The Netherlands
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Affiliation as printed
School of Biodiversity, One Health and Veterinary Medicine, University of Glasgow
School of Biodiversity, One Health and Veterinary Medicine, University of Glasgow, Jarrett Building, G61 1QH Glasgow, United Kingdom
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Affiliation as printed
ZF-screens B.V., J.H. Oortweg 19
ZF-screens B.V., J.H. Oortweg 9, 2333 CH Leiden, The Netherlands
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Affiliation as printed
ZF-screens B.V., J.H. Oortweg 19
ZF-screens B.V., J.H. Oortweg 9, 2333 CH Leiden, The Netherlands
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Affiliation as printed
Medical and Biological Sciences Building, University of St Andrews
Medical and Biological Sciences Building, University of St Andrews, North Haugh, St Andrews, Fife KY16 9TF, UK
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Affiliation as printed
Institute of Biology, Leiden University
Institute of Biology, Leiden University, 2333 CC Leiden, The Netherlands
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Leiden University Medical Center
Affiliation as printed
Department of Infectious Diseases, Leiden University Medical Center
Department of Infectious Diseases, Leiden University Medical Center, 300 RC Leiden, The Netherlands
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Affiliation as printed
ZF-screens B.V., J.H. Oortweg 19
ZF-screens B.V., J.H. Oortweg 9, 2333 CH Leiden, The Netherlands
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Affiliation as printed
Institute of Biology, Leiden University
Institute of Biology, Leiden University, 2333 CC Leiden, The Netherlands
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